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Blood, 15 August 2003, Vol. 102, No. 4, pp. 1550-1551
CORRESPONDENCE
To the editor:
Evaluating the relevance of the platelet transcriptome
A recent article in Blood by Gnatenko et al1 globally profiled mRNA expression in platelets. Using microarray analysis, the authors reported that approximately 2000 transcripts (13%-17% of probed genes) are present in unstimulated platelets isolated from healthy human subjects and concluded that evaluating the platelet transcriptome will be useful for identifying proteins that regulate normal and pathologic platelet and megakaryocyte functions. We have also found similar transcript profiles in platelets with different microarray strategies.2,3
An accompanying commentary voiced similar conclusions, but also suggested that the most frequent platelet mRNAs detected by microarray are well-known leukocyte or red cell messages, heightening suspicion that their abundance may be due to contamination by these classes.4 These 3 messages were thymosin  4, neurogranin, and -globin.1 Thymosin 4 and neurogranin protein are also found in platelets,1,5 however, which is consistent with observations that platelets express gene products that are also present in other cell lineages.2,3,6,7 Moreover, Gnatenko et al1 took rigorous measures to account for contributions by leukocytes and red blood cells, and provided persuasive evidence that the thymosin 4 and neurogranin transcripts are derived from platelets. The significance of detecting -globin mRNA in their preparations still needs to be resolved, and if platelet-derived, will likely require confirmation by in situ detection methods. However, Gnatenko and colleagues indirectly addressed this issue by isolating total RNA from whole blood and concluded that the globin transcripts observed in their platelet preparations were not supported by erythrocyte contaminant estimates.1
Based on serial analysis of gene expression (SAGE) results, which preferentially targets abundant mRNAs, the commentary also underscored the author's conclusions that the vast majority of messages in platelets are mitochondrially derived.1,4 We do not argue this point. Indeed, mitochondrial RNAs are continuously transcribed, in contrast to other platelet transcripts, and generate multiple polyadenylated transcripts from individual genes accounting for their enhanced detection by SAGE.1 An important point, however, is that the mitochondrial genome encodes only 13 mRNAs and 2 rRNAs.1 Platelets contain over 2000 individual mRNA species,1-3 including well-known messages for the  IIb and 3 integrin subunits,8,9 that were not detected by SAGE.1 Thus, although they are more abundant, mitochondrially derived transcripts represent a minute fraction (< 0.01%) of the mRNA species pool present in human platelets.1-3 There are numerous examples in which the identification of nonmitochondrial mRNAs in platelets has generated important physiologic insights regarding the characterization and functional significance of corresponding proteins.1-3,6,7,9,10
Although the total RNA in human platelets is at least 100-fold less than in leukocytes,10 platelet mRNAs are diverse, polyadenylated, distributed in a fashion that is influenced by cytoskeletal and RNA-binding proteins, and differentially translated in response to outside-in signals.1-3,6-8,10 In addition to mitochondrial transcripts, many others are basally present.1-3,6-10 Characterization of the platelet transcriptome, and the proteins that it encodes, will undoubtedly increase our understanding of platelet and megakaryocyte physiology and behavior in health and disease.
Andrew S. Weyrich, and
Guy A. Zimmerman
Correspondence: Andrew S. Weyrich, University of Utah, Department of Internal Medicine, Eccles Institute of Human Genetics, 15 North 2030 East, Bldg 533, Rm 4220, Salt Lake City, UT 84112; e-mail: andy.weyrich{at}hmbg.utah.edu
References
- Gnatenko DV, Dunn JJ, McCorkle SR, Weissmann D, Perrotta PL, Bahou WF. Transcript profiling of human platelets using microarray and serial analysis of gene expression. Blood. 2003;101: 2285-2293.[Abstract/Free Full Text]
- Lindemann S, Tolley ND, Dixon DA, et al. Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. J Cell Biol. 2001;154: 485-490.[Abstract/Free Full Text]
- Lindemann S, Tolley ND, Eyre JR, Kraiss LW, Mahoney TM, Weyrich AS. Integrins regulate the intracellular distribution of eukaryotic initiation factor 4E in platelets: a checkpoint for translational control. J Biol Chem. 2001;276: 33947-33951.[Abstract/Free Full Text]
- Poncz M. Platelet message and microarrays. Blood. 2003;101: 2078.[Free Full Text]
- Huff T, Otto AM, Muller CS, Meier M, Hannappel E. Thymosin beta4 is released from human blood platelets and attached by factor XIIIA (transglutaminase) to fibrin and collagen. Faseb J. 2002;16: 691-696.[Abstract/Free Full Text]
- Schmidt VA, Nierman WC, Maglott DR, et al. The human proteinase-activated receptor-3 (par-3) gene: identification within a par gene cluster and characterization in vascular endothelial cells and platelets. J Biol Chem. 1998;273: 15061-15068.[Abstract/Free Full Text]
- Clemetson KJ, Clemetson JM, Proudfoot AE, Power CA, Baggiolini M, Wells TN. Functional expression of CCR1, CCR3, CCR4, and CXCR4 chemokine receptors on human platelets. Blood. 2000;96: 4046-4054.[Abstract/Free Full Text]
- Burk CD, Newman PJ, Lyman S, Gill J, Coller BS, Poncz M. A deletion in the gene for glycoprotein IIb associated with Glanzmann's thrombasthenia. J Clin Invest. 1991;87: 270-276.[Medline]
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- Newman PJ, Gorski J, White GC II, Gidwitz S, Cretney CJ, Aster RH. Enzymatic amplification of platelet-specific messenger RNA using the polymerase chain reaction. J Clin Invest. 1988;82: 739-743.[Medline]
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- Sottile J, Mosher DF, Fullenweider J, George JN. Human platelets contain mRNA transcripts for platelet factor 4 and actin. Thromb Haemost. 1989;62: 1100-1102.[Medline]
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Transcript profiling of human platelets using microarray and serial analysis of gene expression
- Dmitri V. Gnatenko, John J. Dunn, Sean R. McCorkle, David Weissmann, Peter L. Perrotta, and Wadie F. Bahou
Blood 2003 101: 2285-2293.
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